Background: Among patients with Charcot–Marie–Tooth disease (CMT), the X-linked variant (CMTX) caused by gap junction protein beta 1 (GJB1) gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 (CX32). CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered.
Methods: We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People's Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX1.
Results: Nine GJB1 mutations (c.283G>A, c.77C>T, c.643C>T, c.515C>T, c.191G>A, c.610C>T, c.490C>T, c.491G>A, and c.44G>A) were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were < 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C>T, c.191G>A, and c.610C>T, were revealed and bioinformatics analyses indicated high pathogenicity.
Conclusions: The three novel missense mutations within the GJB1 gene broaden the mutational diversity of CMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.
Methods: A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited. Clinical features were evaluated, and all subjects were screened for MR-1, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia, and myotonia congenita (MC), respectively. In addition, 200 genetically matched healthy individuals were recruited as controls.
Results: A total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G>A mutation was detected in one case, and CLCN1 c.1205C>T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A1 c.363G>A mutation was novel.
Conclusions: The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2- negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.

Background: Deep brain stimulation (DBS) has been a promising treatment for patients with refractory Tourette syndrome (TS) for more than a decade. Despite successful DBS treatment of TS in more than 100 patients worldwide, studies with a large patient sample and long-term follow-up assessments are still scarce. Accordingly, we investigated the clinical efficacy and safety of globus pallidus internus (GPi) DBS in the treatment of intractable TS in 24 patients with a 1-year follow-up assessment.
Methods: Bilateral/unilateral GPi-DBS was performed in 24 patients with TS. We evaluated symptoms of tics and obsessive-compulsive disorder (OCD) through the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive-compulsive Scale (Y-BOCS). We used the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) to evaluate the safety of the treatment. We conducted follow-up assessments of all patients for at least 12 months (12–99 months).
Results: Symptoms of tics and OCD were significantly relieved at a 12-month follow-up assessment. The mean YGTSS score was 74.04 ± 11.52, 49.83 ± 10.91, 32.58 ± 7.97, and 31.21 ± 8.87 at baseline, 3, 6, and 12 months, respectively. The mean YGTSS scores obtained at the follow-up assessments were significantly different from the baseline (P < 0.05). The improvement in motor tics was superior to that in phonic tics. The mean Y-BOCS scores were 21.61 ± 4.97, 18 ± 4.58, 14.39 ± 3.99, and 13.78 ± 4.56 at baseline, 3, 6, and 12 months, respectively (P < 0.05). We observed a remarkable improvement in psychiatric comorbidities, such as OCD and attention-deficit hyperactivity disorder, after the procedure. WAIS-RC scores were comparable before and after the operation. There were no severe postoperative complications.
Conclusion: GPi-DBS appears to comprehensively alleviate tic symptoms and psychiatric comorbidities in patients with TS, thus significantly improving patients' quality of life.

Background: The appropriate elbow position of short-segment nerve conduction study (SSNCS) to diagnose cubital tunnel syndrome (CubTS) is still controversial. The goal of this study was to determine the effect of different elbow positions at full extension and 70° flexion on SSNCS in CubTS.
Methods: In this cross-sectional study, the clinical data of seventy elbows from 59 CubTS patients between September, 2011 and December, 2014 in the Peking University First Hospital were included as CubTS group. Moreover, thirty healthy volunteers were included as the healthy group. SSNCS were conducted in all subjects at elbow full extension and 70° elbow flexion. Paired nonparametric test, bivariate correlation, Bland–Altman, and Chi-squared test analysis were used to compare the effectiveness of elbow full extension and 70° flexion elbow positions on SSNCS in CubTS patients.
Results: Data of upper limit was calculated from healthy group, and abnormal latency was judged accordingly. CubTS group's latency and compound muscle action potential (CMAP) of each segment at 70° elbow flexion by SSNCS was compared with full extension position, no statistically significant difference were found (all P > 0.05). Latency and CMAP of each segment at elbow full extension and 70° flexion were correlated (all P < 0.01), except the latency of segment of 4 cm to 6 cm above elbow (P = 0.43), and the latency (P = 0.15) and the CMAP (P = 0.06) of segment of 2 cm to 4 cm below elbow. Bivariate correlation and Bland–Altman analysis proved the correlation between elbow full extension and 70° flexion. Especially in segments across the elbow (2 cm above the elbow and 2 cm below it), latency at elbow full extension and 70° flexion were strong direct associated (r = 0.83, P < 0.01; r = 0.55, P < 0.01), and so did the CMAP (r = 0.49, P < 0.01; r = 0.72, P < 0.01). There was no statistically significant difference in abnormality of each segment at full extension as measured by SSNCS compared with that at 70° flexion (P > 0.05, respectively).
Conclusions: There was no statistically significant difference in the diagnosis of CubTS with the elbow at full extension compared with that at 70° flexion during SSNCS. We suggest that elbow positon at full extension can also be used during SSNCS.

Background: Single-fiber electromyography (SFEMG) has been suggested as a quantitative method for supporting chronic partial denervation in amyotrophic lateral sclerosis (ALS) by the revised EI Escorial criteria. Although concentric needle (CN) electrodes have been used to assess jitter in myasthenia gravis patients and healthy controls, there are few reports using CN electrodes to assess motor unit instability and denervation in neurogenic diseases. The aim of this study was to determine whether quantitative changes in jitter and spike number using CN electrodes could be used for ALS studies.
Methods: Twenty-seven healthy controls and 23 ALS patients were studied using both CN and single-fiber needle (SFN) electrodes on the extensor digitorum communis muscle with an SFEMG program. The SFN-jitter and SFN-fiber density data were measured using SFN electrodes. The CN-jitter and spike number were measured using CN electrodes.
Results: The mean CN-jitter was significantly increased in ALS patients (47.3 ± 17.0 μs) than in healthy controls (27.4 ± 3.3 μs) (P < 0.001). Besides, the mean spike number was significantly increased in ALS patients (2.5 ± 0.5) than in healthy controls (1.7 ± 0.3) (P < 0.001). The sensitivity and specificity in the diagnosis of ALS were 82.6% and 92.6% for CN-jitter (cut-off value: 32 μs), and 91.3% and 96.3% for the spike number (cut-off value: 2.0), respectively. There was no significant difference between the SFN-jitter and CN-jitter in ALS patients; meanwhile, there was no significant difference between the SFN-jitter and CN-jitter in healthy controls.
Conclusion: CN-jitter and spike number could be used to quantitatively evaluate changes due to denervation-reinnervation in ALS.

Background: Differentiating intracerebral hemorrhage (ICH) from cerebral infarction as early as possible is vital for the timely initiation of different treatments. This study developed an applicable model for the ambulance system to differentiate stroke subtypes.
Methods: From 26,163 patients initially screened over 4 years, this study comprised 1989 consecutive patients with potential first-ever acute stroke with sudden onset of the focal neurological deficit, conscious or not, and given ambulance transport for admission to two county hospitals in Yutian County of Hebei Province. All the patients underwent cranial computed tomography (CT) or magnetic resonance imaging to confirm the final diagnosis based on stroke criteria. Correlation with stroke subtype clinical features was calculated and Bayes' discriminant model was applied to discriminate stroke subtypes.
Results: Among the 1989 patients, 797, 689, 109, and 394 received diagnoses of cerebral infarction, ICH, subarachnoid hemorrhage, and other forms of nonstroke, respectively. A history of atrial fibrillation, vomiting, and diabetes mellitus were associated with cerebral infarction, while vomiting, systolic blood pressure ≥180 mmHg, and age <65 years were more typical of ICH. For noncomatose stroke patients, Bayes' discriminant model for stroke subtype yielded a combination of multiple items that provided 72.3% agreement in the test model and 79.3% in the validation model; for comatose patients, corresponding agreement rates were 75.4% and 73.5%.
Conclusions: The model herein presented, with multiple parameters, can predict stroke subtypes with acceptable sensitivity and specificity before CT scanning, either in alert or comatose patients. This may facilitate prehospital management for patients with stroke.

Background: Proteasome subunits (PSMB) and transporter associated with antigen processing (TAP) loci are located in the human leukocyte antigen (HLA) Class II region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of PSMB and TAP and Parkinson's disease (PD).
Methods: A case–control study was conducted by genotyping SNPs in PSMB8, PSMB9, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMB9, TAP1, and TAP2 were genotyped through SNaPshot testing.
Results: The stratified analysis of rs17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rs17587-G/G versus (A/A + G/A) compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients.
Conclusion: Chinese females carrying the rs17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD.

Background: The one-step method was routine practices in China, scientific evidence to support this intervention is scarce. The purpose of this study was to observe the natural process of head-to-body delivery interval by waiting for at least one contraction (two-step) after head delivered in normal birth.
Methods: From March 1 to March 30 in 2015 at Haikou Maternal and Child Hospital in China, normal vaginal birth with normal baby condition were recorded by video. Videotapes were transferred to computer then replayed and observed.
Results: Ninety-two cases were enrolled in this study. The average head-to-body delivery interval by two-step delivery was 71.04 ± 61.02 s, (mean + 2 standard deviation = 193.07 s, 95% confidence interval [15.65–229.15] s). Fifty-one patients (51/92, 55.43%) were <60 s, 41 patients (41/92, 44.57%) were over 60 s. Shoulders delivered at the first contraction were 96.74% (89/92), 3.26% (3/92) had delivered by the second contraction. Shoulders emerged from perineum were 71.73% (66/92), 15.21% (14/92) transversely, and 13.04% (12/92) emerged from under pubic arch. Babies cried before the shoulder were 31.52% (29/92), cried after birth 52.17% (48/92), and 16.30% (15/92) did not cry after birth. Baby activities included as making faces, sucking, and bubbled from mouth and noses, and the lighter blue color of skin with good perfusion.
Conclusions: The average time of head-to-body delivery interval was longer than 60 s by two-step delivery. Majority shoulders were delivered at the first contraction. Majority shoulders emerged from perineum rather from under pubic arch. The routine one-step method of shoulder delivery where the downward force applied is not necessary and is not the right direction. Baby's breath, making faces, sucking, bubble from noses and mouth, and the light blue color of the faces, all those signs during shoulder delivery indicated a normal live birth.

Background: Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid β-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This study aimed to discover more mutations and provide data for the genetic pattern of the gene, which will help the development of quick and accurate genetic diagnostic tools for this disease.
Methods: Genomic DNA was obtained from peripheral blood leukocytes of the patient and Sanger sequencing is used to sequence GBA gene. Sequence alignments of mammalian β-GBA (GCase) and three-dimensional protein structure prediction of the mutation were made. A construct of this mutant and its compound heterozygous counterpart were used to measure GCase in vitro.
Results: GCase is relatively conserved at p.T219A. This novel mutation differs from its wild-type in structure. Moreover, it also causes a reduction in GCase enzyme activity.
Conclusion: This novel mutation (c.655A>G, p.T219A) is a pathogenic missense mutation, which contributes to GD.

Background: This study was to establish a disease differentiation model for ST-segment elevation myocardial infarction (STEMI) youth patients experiencing ischemia and reperfusion via ultra-performance liquid chromatography and mass spectrometry (UPLC/MS) platform, which searches for closely related characteristic metabolites and metabolic pathways to evaluate their predictive value in the prognosis after discharge.
Methods: Forty-seven consecutive STEMI patients (23 patients under 45 years of age, referred to here as “youth,” and 24 “elderly” patients) and 48 healthy control group members (24 youth, 24 elderly) were registered prospectively. The youth patients were required to provide a second blood draw during a follow-up visit one year after morbidity (n = 22, one lost). Characteristic metabolites and relative metabolic pathways were screened via UPLC/MS platform base on the Kyoto encyclopedia of genes and genomes (KEGG) and Human Metabolome Database. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of characteristic metabolites in the prognosis after discharge.
Results: We successfully established an orthogonal partial least squares discriminated analysis model (R2X = 71.2%, R2Y = 79.6%, and Q2 = 55.9%) and screened out 24 ions; the sphingolipid metabolism pathway showed the most drastic change. The ROC curve analysis showed that ceramide [Cer(d18:0/16:0), Cer(t18:0/12:0)] and sphinganine in the sphingolipid pathway have high sensitivity and specificity on the prognosis related to major adverse cardiovascular events after youth patients were discharged. The area under curve (AUC) was 0.671, 0.750, and 0.711, respectively. A follow-up validation one year after morbidity showed corresponding AUC of 0.778, 0.833, and 0.806.
Conclusions: By analyzing the plasma metabolism of myocardial infarction patients, we successfully established a model that can distinguish two different factors simultaneously: pathological conditions and age. Sphingolipid metabolism is the top most altered pathway in young STEMI patients and as such may represent a valuable prognostic factor and potential therapeutic target.

Background: Optical coherence tomography (OCT) angiography is a novel technique by which we can detect the local perfusion of fundus directly. The aim of this study was to evaluate the reproducibility of optic disc and macular flow perfusion parameters in rhesus monkeys using OCT angiography.
Methods: Eighteen healthy monkeys (18 eyes) were subjected to optic disc and macula flow index measurements via a high-speed and high-resolution spectral-domain OCT XR Avanti with a split-spectrum amplitude de-correlation angiography algorithm. Right eye was imaged 3 times during the first examination and once during each of the two following examinations. The intra-visit and inter-visit intraclass correlation coefficients (ICCs) were both determined.
Results: The average flow indices of the four optic disc area layers were 0.171 ± 0.009 (optic nerve head), 0.015 ± 0.004 (vitreous), 0.052 ± 0.009 (radial peripapillary capillary), and 0.167 ± 0.011 (choroid). Average flow indices of the four macula area layers were 0.044 ± 0.011 (superficial retina), 0.036 ± 0.011 (deep retina), 0.016 ± 0.009 (outer retina), and 0.155 ± 0.013 (choroid). Intra-visit (ICC value: 0.821–0.954) and inter-visit (ICC value: 0.844–0.899) repeatability were both high.
Conclusions: The study is about the reproducibility of optic disc and macular perfusion parameters as measured by OCT angiography in healthy rhesus monkeys. Flow index measurement reproducibility is high for both the optic disc and macula of normal monkey eyes. OCT angiography might be a useful technique to assess changes when examining monkeys with experimental ocular diseases.

Background: The ability to predict posttraumatic stress disorder (PTSD) is a critical issue in the management of patients with mild traumatic brain injury (mTBI), as early medical and rehabilitative interventions may reduce the risks of long-term cognitive changes. The aim of the present study was to investigate how diffusion tensor imaging (DTI) metrics changed in the transition from acute to chronic phases in patients with mTBI and whether the alteration relates to the development of PTSD.
Methods: Forty-three patients with mTBI and 22 healthy volunteers were investigated. The patients were divided into two groups: successful recovery (SR, n = 22) and poor recovery (PR, n = 21), based on neurocognitive evaluation at 1 or 6 months after injury. All patients underwent magnetic resonance imaging investigation at acute (within 3 days), subacute (10–20 days), and chronic (1–6 months) phases after injury. Group differences of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed using tract-based spatial statistics (TBSS). The accuracy of DTI metrics for classifying PTSD was estimated using Bayesian discrimination analysis.
Results: TBSS showed white matter (WM) abnormalities in various brain regions. In the acute phase, FA values were higher for PR and SR patients than controls (all P < 0.05). In subacute phase, PR patients have higher mean MD than SR and controls (all P < 0.05). In the chronic phase, lower FA and higher MD were observed in PR compared with both SR and control groups (all P < 0.05). PR and SR groups could be discriminated with a sensitivity of 73%, specificity of 78%, and accuracy of 75.56%, in terms of MD value in subacute phase.
Conclusions: Patients with mTBI have multiple abnormalities in various WM regions. DTI metrics change over time and provide a potential indicator at subacute stage for PTSD following mTBI.

Background: Resolvin D1 (RvD1) is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanism.
Methods: Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group (saline), LPS group (LPS 5 mg/kg), RvD1 group (RvD1 5 μg/kg + LPS 5 mg/kg), and blockage group (Boc-MLP 5 μg/kg + RvD1 5 μg/kg + LPS 5 mg/kg). Boc-MLP is a RvD1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively (n = 6 in each group at each time point). Human proximal tubule epithelial cells (HK-2) were randomly divided into control group (medium only), LPS group (LPS 5 μg/ml), RvD1 group (RvD1 10 ng/ml + LPS 5 μg/ml), and blockage group (Boc-MLP 10 ng/ml + RvD1 10 ng/ml + LPS 5 μg/ml). The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively (n = 6 in each group at each time point). Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α (TNF-α) level was detected by ELISA. Kidney pathology was observed under hematoxylin and eosin (HE) staining and transmission electron microscope (TEM). We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B (NF-κB) signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining.
Results: RvD1 receptor ALX was detected on renal tubular epithelials. Kaplan–Meier analysis indicated that RvD1 improved 48 h animal survival (80%) compared with LPS group (40%) and RvD1 blockage group (60%), while RvD1 also ameliorated kidney pathological injury in HE staining and TEM scan. After LPS stimulation, the mRNA expression of toll-like receptor 4, myeloid differentiation factor 88, and TNF-α in both mice kidneys and HK-2 cells were all up-regulated, while RvD1 substantially inhibited the up-regulation of these genes. Western blotting showed that the phosphorylated-IκB/IκB ratio in LPS group was significantly higher than that in the control group, which was inhibited in the RvD1 group. RvD1 could inhibit the up-regulation of cleaved-caspase-3 protein stimulated by LPS, which was prohibited in RvD1 blockage group. RvD1 group also had a lower proportion of apoptotic nuclei in mice kidney by TUNEL staining compared with LPS group.
Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-κB inflammatory signal as well as inhibiting renal cell apoptosis.

Background: Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein-1 (MCP-1). Oxidized low-density lipoprotein (oxLDL) participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinflammatory function of oxLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L1 adipocytes induced by oxLDL and to elucidate the possible mechanisms.
Methods: Fully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentration of L-4F (0–50 μg/ml) with oxLDL (50 μg/ml) stimulated, with/without protein kinase A (PKA) inhibitor H-89 (10 μmol/L) preincubated. The concentrations of MCP-1 in the supernatant, the mRNA expression of MCP-1, the levels of CCAAT/enhancer binding protein α (C/EBPα), and CCAAT/enhancer binding protein β (C/EBPβ) were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber.
Results: OxLDL stimulation induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F (50 μg/ml) (P > 0.05). OxLDL stimulation showed no significant effect on C/EBPα protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPβ protein level in oxLDL-induced 3T3-L1 adipocytes.
Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.